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1.
Int J Mol Sci ; 25(9)2024 Apr 30.
Article En | MEDLINE | ID: mdl-38732122

Osteoarthritis is more prevalent than any other form of arthritis and is characterized by the progressive mechanical deterioration of joints. Glucosamine, an amino monosaccharide, has been used for over fifty years as a dietary supplement to alleviate osteoarthritis-related discomfort. Silibinin, extracted from milk thistle, modifies the degree of glycosylation of target proteins, making it an essential component in the treatment of various diseases. In this study, we aimed to investigate the functional roles of glucosamine and silibinin in cartilage homeostasis using the TC28a2 cell line. Western blots showed that glucosamine suppressed the N-glycosylation of the gp130, EGFR, and N-cadherin proteins. Furthermore, both glucosamine and silibinin differentially decreased and increased target proteins such as gp130, Snail, and KLF4 in TC28a2 cells. We observed that both compounds dose-dependently induced the proliferation of TC28a2 cells. Our MitoSOX and DCFH-DA dye data showed that 1 µM glucosamine suppressed mitochondrial reactive oxygen species (ROS) generation and induced cytosol ROS generation, whereas silibinin induced both mitochondrial and cytosol ROS generation in TC28a2 cells. Our JC-1 data showed that glucosamine increased red aggregates, resulting in an increase in the red/green fluorescence intensity ratio, while all the tested silibinin concentrations increased the green monomers, resulting in decreases in the red/green ratio. We observed increasing subG1 and S populations and decreasing G1 and G2/M populations with increasing amounts of glucosamine, while increasing amounts of silibinin led to increases in subG1, S, and G2/M populations and decreases in G1 populations in TC28a2 cells. MTT data showed that both glucosamine and silibinin induced cytotoxicity in TC28a2 cells in a dose-dependent manner. Regarding endoplasmic reticulum stress, both compounds induced the expression of CHOP and increased the level of p-eIF2α/eIF2α. With respect to O-GlcNAcylation status, glucosamine and silibinin both reduced the levels of O-GlcNAc transferase and hypoxia-inducible factor 1 alpha. Furthermore, we examined proteins and mRNAs related to these processes. In summary, our findings demonstrated that these compounds differentially modulated cellular proliferation, mitochondrial and cytosol ROS generation, the mitochondrial membrane potential, the cell cycle profile, and autophagy. Therefore, we conclude that glucosamine and silibinin not only mediate glycosylation modifications but also regulate cellular processes in human chondrocytes.


Chondrocytes , Glucosamine , Homeostasis , Kruppel-Like Factor 4 , Reactive Oxygen Species , Silybin , Glucosamine/pharmacology , Glucosamine/metabolism , Humans , Silybin/pharmacology , Glycosylation/drug effects , Chondrocytes/metabolism , Chondrocytes/drug effects , Homeostasis/drug effects , Reactive Oxygen Species/metabolism , Kruppel-Like Factor 4/metabolism , Cell Line , Cell Proliferation/drug effects , Mitochondria/metabolism , Mitochondria/drug effects , Cartilage/metabolism , Cartilage/drug effects , Oxidative Stress/drug effects , Osteoarthritis/metabolism , Osteoarthritis/drug therapy
2.
Eur Radiol ; 34(3): 1764-1773, 2024 Mar.
Article En | MEDLINE | ID: mdl-37658138

OBJECTIVES: To assess the performance of MRI scale for the diagnosis of acute appendicitis in pregnant women and to determine the added diagnostic value of diffusion-weighted imaging (DWI). METHODS: From January 2018 to December 2020, 80 patients were included. All MRI were performed with a 1.5-Tesla scanner with anterior array body coil. This analysis included (1) T2-weighted imaging (T2WI), (2) fat-saturated T2WI, and (3) DWI. Two radiologists blinded to the diagnosis recorded their assessment of four findings: appendiceal diameter, appendiceal wall thickness, luminal mucus, and periappendiceal inflammation. The MRI scale of acute appendicitis which ranged from 0 to 4 was determined from these factors. An additional one point was added to the MRI appendicitis scale in those patients with evidence of appendiceal restricted diffusion on DWI. The diagnostic values and predictive factors were computed. RESULTS: Multivariate analysis demonstrated that the calculated MRI appendicitis scale was a significant independent predictor of acute appendicitis with a sensitivity of 96.6%, specificity of 90.2%, and PPV of 84.8%. The odds ratio of appendicitis is increased by 22.3 times for every increase in one point on the MRI appendicitis scale. Therefore, the addition of one point for restricted diffusion in the appendix on DWI imaging can add substantial value, both positive and negative predictive value, towards making an accurate diagnosis of acute appendicitis. CONCLUSIONS: MRI appendicitis scale is an objective and significant independent predictive factor for acute appendicitis in pregnant women. Incorporation of diffusion weighted imaging to MRI can improve diagnosis of acute appendicitis. CLINICAL RELEVANCE STATEMENT: MRI appendicitis scale is an objective and significant independent predictor of acute appendicitis in pregnant women. Incorporation of DWI/ADC map to MRI examinations can improve diagnosis of acute appendicitis in pregnant women. KEY POINTS: • MRI appendicitis scale is an objective and significant independent predictive factor for acute appendicitis in pregnant women. • The odds ratio of appendicitis can be increased by 22.3 times for every increase of one unit in MRI scale. • Incorporation of diffusion-weighted imaging to MRI examinations can add value to the scale (4.2 ± 0.7 vs. 0.7 ± 1.1; p < 0.001) among pregnant women with appendicitis versus pregnant women without appendicitis.


Appendicitis , Humans , Female , Pregnancy , Appendicitis/diagnostic imaging , Pregnant Women , Diagnosis, Differential , Magnetic Resonance Imaging/methods , Diffusion Magnetic Resonance Imaging/methods , Acute Disease , Sensitivity and Specificity , Retrospective Studies
3.
Mol Biol Rep ; 49(12): 12007-12015, 2022 Dec.
Article En | MEDLINE | ID: mdl-36273336

BACKGROUND: Interferon-gamma (IFN-γ) is an immune-derived cytokines in the innate and adaptive immune responses, and functions as a major pro-inflammatory cytokine. IFNγ has previously been reported involving in the regulation of bone metabolism. However, contradictory results about the roles of IFN-γ in bone formation or bone resorption have been reported. It is possible that the functions of IFN-γ in bone formation is dose-dependent or time-dependent. In this study we examined the effect of IFN-γ on different stages of osteoblastogenesis and bone formation. MATERIALS AND METHODS: Cell proliferation, gene expression and protein levels of the critical effectors involving in different stages of differentiation were compared between differentiating preosteoblast MC3T3-E1 treated with or without IFN-γ at different stages. Cell proliferation were determined by MTT assay. Expression levels of osteoblast differentiation markers was performed by quantitative PCR assay. Also, western blot was conducted to investigate the protein levels in those effectors. CONCLUSION: IFN-γ regulates osteoblast and bone formation in a stage-dependent manner. IFN-γ did not alter and the expression of critical osteogenic transcription factors, such as Runx2 and Cbfb, suggesting that the differentiation was not disrupted by IFN-γ. The cell number and the levels of matrix proteins, including COL1A and BSP, at both early and late stage of osteoblastogenesis were downregulated by IFN-γ, indicating its negative regulating roles in early stages. In contrast, the mineralization protein ALP and OCN was upregulated at late stages. The results suggested that IFN-γ might act as a negative regulator in osteoblast differentiation and bone formation at early stages but switch into positive regulator at late stage. Our data revealed the complex features of the effects of IFN-γ on osteoblast differentiation. The detailed mechanisms of how IFN-γ influence on the bone formation and balance of bone remodeling will be further studied.


Bone Resorption , Osteogenesis , Humans , Interferon-gamma/pharmacology , Interferon-gamma/metabolism , Core Binding Factor Alpha 1 Subunit/genetics , Core Binding Factor Alpha 1 Subunit/metabolism , Osteoblasts , Bone Resorption/metabolism , Bone Remodeling , Cell Differentiation
4.
Gels ; 8(3)2022 Feb 27.
Article En | MEDLINE | ID: mdl-35323262

The generation of hepatic spheroids is beneficial for a variety of potential applications, including drug development, disease modeling, transplantation, and regenerative medicine. Natural hydrogels are obtained from tissues and have been widely used to promote the growth, differentiation, and retention of specific functionalities of hepatocytes. However, relying on natural hydrogels for the generation of hepatic spheroids, which have batch to batch variations, may in turn limit the previously mentioned potential applications. For this reason, we researched a way to establish a three-dimensional (3D) culture system that more closely mimics the interaction between hepatocytes and their surrounding microenvironments, thereby potentially offering a more promising and suitable system for drug development, disease modeling, transplantation, and regenerative medicine. Here, we developed self-assembling and bioactive hybrid hydrogels to support the generation and growth of hepatic spheroids. Our hybrid hydrogels (PC4/Cultrex) inspired by the sandcastle worm, an Arg-Gly-Asp (RGD) cell adhesion sequence, and bioactive molecules derived from Cultrex BME (Basement Membrane Extract). By performing optimizations to the design, the PC4/Cultrex hybrid hydrogels can enhance HepG2 cells to form spheroids and express their molecular signatures (e.g., Cyp3A4, Cyp7a1, A1at, Afp, Ck7, Ck1, and E-cad). Our study demonstrated that this hybrid hydrogel system offers potential advantages for hepatocytes in proliferating, differentiating, and self-organizing to form hepatic spheroids in a more controllable and reproducible manner. In addition, it is a versatile and cost-effective method for 3D tissue cultures in mass quantities. Importantly, we demonstrate that it is feasible to adapt a bioinspired approach to design biomaterials for 3D culture systems, which accelerates the design of novel peptide structures and broadens our research choices on peptide-based hydrogels.

5.
Mol Biol Rep ; 49(5): 3927-3937, 2022 May.
Article En | MEDLINE | ID: mdl-35218446

BACKGROUND: Clinical data and phenotypes of several in vivo models demonstrated that interleukin-6 (IL-6) is an essential positive regulator in inflammation-induced bone loss. However, how IL-6 affect bone resorption and the osteoclast differentiation remains in debate. In this study we elucidate the cellular responses of receptor activator of nuclear factor kappa-Β ligand (RANKL)-stimulated RAW254.7 macrophage, the process mimicking osteoclast differentiation, upon IL-6 co-stimulation. IL-6 is a pleiotropic cytokine triggering various cellular responses, ranging from pro-inflammatory responses, differentiation to proliferation or apoptosis in different cell types. Those cellular events in the RANKL-stimulated RAW cells were examined to understand how differentiating monocytic cells respond to IL-6 exposure. MATERIALS AND METHODS: Proliferation, apoptosis, differentiation and Pro-inflammatory responses of RANKL-stimulated RAW254.7 macrophage treated with or without IL-6 were measured by MTT assay, quantitative PCR assay of the expression of apoptotic genes, osteoclast differentiation markers, and pro-inflammatory genes, respectively. The results were collected from different time points in a 6-day differentiation period. Also, western blot on STAT3, ERK and AKT were also performed to investigate the IL-6 signaling in those cells. CONCLUSIONS: IL-6 triggered transient proliferation, but not apoptosis, in RANKL-stimulated RAW cells. Osteoclastogenesis was disrupted as the expression of essential genes for bone resorption were inhibited, and the osteoclast precursors maintained their undifferentiated phenotypes, with pro-inflammatory genes upregulated. Our results suggested that IL-6 interferes osteoclastogenesis. Additionally, IL-6 promote pro-inflammatory responses of monocytic cells and aggravate inflammation.


Bone Resorption , Interleukin-6 , Osteoclasts , Bone Resorption/genetics , Bone Resorption/metabolism , Cell Differentiation , Cell Proliferation , Humans , Inflammation , Inflammation Mediators/metabolism , Interleukin-6/metabolism , NF-kappa B/metabolism , Osteoclasts/cytology , Osteoclasts/metabolism , Osteogenesis , RANK Ligand/metabolism , RANK Ligand/pharmacology
6.
Surg Endosc ; 35(12): 6623-6632, 2021 12.
Article En | MEDLINE | ID: mdl-33258028

BACKGROUND: Acute cholecystitis (AC) is a common surgical emergency. The Tokyo Guidelines 2018 (TG18) provides a reliable algorithm for the treatment of AC patients to achieve optimal outcomes. However, the economic benefits have not been validated. We hypothesize that good outcomes and cost savings can both be achieved if patients are treated according to the TG18. METHOD: This retrospective study included 275 patients who underwent cholecystectomy in a 15-month span. Patients were divided into three groups (group 1: mild AC; group 2: moderate AC with American Society of Anesthesiologists (ASA) physical status class ≤ 2 and Charlson Comorbidity Index (CCI) score ≤ 5; and group 3: moderate AC with ASA class ≥ 3, CCI score ≥ 6, or severe AC). Each group was further divided into two subgroups according to management (followed or deviated from the TG18). Patient demographics, clinical outcomes, and hospital costs were compared. RESULTS: For group 1 patients, 77 (81%) were treated according to the TG18 and had a significantly higher successful laparoscopic cholecystectomy (LC) rate (100%), lower hospital cost ($1896 vs $2388), and shorter hospital stay (2.9 vs 8 days) than those whose treatment deviated from the TG18. For group 2 patients, 50 (67%) were treated according to the TG18 and had a significantly lower hospital cost ($1926 vs $2856), shorter hospital stay (3.9 vs 9.9 days), and lower complication rate (0% vs 12.5%). For group 3 patients, 62 (58%) were treated according to the TG18 and had a significantly lower intensive care unit (ICU) admission rate (9.7% vs 25%), but a longer hospital stay (12.6 vs 7.8 days). However, their hospital costs were similar. Early LC in group 3 patients did not have economic benefits over gallbladder drainage and delayed LC. CONCLUSION: The TG18 are the state-of-the-art guidelines for the treatment of AC, achieving both satisfactory outcomes and cost-effectiveness.


Cholecystectomy, Laparoscopic , Cholecystitis, Acute , Cholecystitis, Acute/surgery , Health Expenditures , Humans , Length of Stay , Retrospective Studies , Tokyo , Treatment Outcome
7.
Sci Rep ; 10(1): 19612, 2020 11 12.
Article En | MEDLINE | ID: mdl-33184342

Massive hepatic necrosis after therapeutic embolization has been reported. We employed a 320-detector CT scanner to compare liver perfusion differences between blunt liver trauma patients treated with embolization and observation. This prospective study with informed consent was approved by institution review board. From January 2013 to December 2016, we enrolled 16 major liver trauma patients (6 women, 10 men; mean age 34.9 ± 12.8 years) who fulfilled inclusion criteria. Liver CT perfusion parameters were calculated by a two-input maximum slope model. Of 16 patients, 9 received embolization and 7 received observation. Among 9 patients of embolization group, their arterial perfusion (78.1 ± 69.3 versus 163.1 ± 134.3 mL/min/100 mL, p = 0.011) and portal venous perfusion (74.4 ± 53.0 versus 160.9 ± 140.8 mL/min/100 mL, p = 0.008) were significantly lower at traumatic parenchyma than at non-traumatic parenchyma. Among 7 patients of observation group, only portal venous perfusion was significantly lower at traumatic parenchyma than non-traumatic parenchyma (132.1 ± 127.1 vs. 231.1 ± 174.4 mL/min/100 mL, p = 0.018). The perfusion index between groups did not differ. None had massive hepatic necrosis. They were not different in age, injury severity score and injury grades. Therefore, reduction of both arterial and portal venous perfusion can occur when therapeutic embolization was performed in preexisting major liver trauma, but hepatic perfusion index may not be compromised.


Embolization, Therapeutic/methods , Liver/diagnostic imaging , Liver/injuries , Perfusion Imaging/methods , Wounds, Nonpenetrating/diagnostic imaging , Wounds, Nonpenetrating/therapy , Adult , Embolization, Therapeutic/adverse effects , Female , Hepatic Artery , Humans , Male , Massive Hepatic Necrosis/diagnostic imaging , Massive Hepatic Necrosis/etiology , Middle Aged , Perfusion , Portal Vein , Prospective Studies , Tomography, X-Ray Computed , Young Adult
8.
J Med Internet Res ; 22(8): e17686, 2020 08 28.
Article En | MEDLINE | ID: mdl-32857060

BACKGROUND: The application of mobile health (mHealth) platforms to monitor recovery in the postdischarge period has increased in recent years. Despite widespread enthusiasm for mHealth, few studies have evaluated the usability and user experience of mHealth in patients with surgical drainage. OBJECTIVE: Our objectives were to (1) develop an image-based smartphone app, SurgCare, for postdrainage monitoring and (2) determine the feasibility and clinical value of the use of SurgCare by patients with drainage. METHODS: We enrolled 80 patients with biliary or peritoneal drainage in this study. A total of 50 patients were assigned to the SurgCare group, who recorded drainage monitoring data with the smartphone app; and 30 patients who manually recorded the data were assigned to the conventional group. The patients continued to record data until drain removal. The primary aim was to validate feasibility for the user, which was defined as the proportion of patients using each element of the system. Moreover, the secondary aim was to evaluate the association of compliance with SurgCare and the occurrence of unexpected events. RESULTS: The average submission duration was 14.98 days, and the overall daily submission rate was 84.2%. The average system usability scale was 83.7 (SD 3.5). This system met the definition of "definitely feasible" in 34 patients, "possibly feasible" in 10 patients, and "not feasible" in 3 patients. We found that the occurrence rates of complications in the SurgCare group and the conventional group were 6% and 26%, respectively, with statistically significant differences P=.03. The rate of unexpected hospital return was lower in the SurgCare group (6%) than in the conventional groups (26%) (P=.03). CONCLUSIONS: Patients can learn to use a smartphone app for postdischarge drainage monitoring with high levels of user satisfaction. We also identified a high degree of compliance with app-based drainage-recording design features, which is an aspect of mHealth that can improve surgical care.


Aftercare/methods , Drainage/methods , Mobile Applications/standards , Telemedicine/methods , User-Centered Design , Adult , Female , Humans , Male , Young Adult
9.
Chin J Physiol ; 62(2): 70-79, 2019.
Article En | MEDLINE | ID: mdl-31243177

Glucocorticoid-induced bone loss is the most common form of secondary osteoporosis. This toxic effect has not been efficiently managed, possibly due to the incomplete understanding of the extraordinarily diverse cellular responses induced by glucocorticoid treatment. Previous literatures revealed that high dose of exogenous glucocorticoid triggers apoptosis in osteocytes and osteoblasts. This cell death is associated with glucocorticoid-induced oxidative stress. In this study, we aimed to investigate the mechanisms of glucocorticoid-induced apoptosis in osteoblasts and examine the responses of osteoclasts to the synthetic glucocorticoid, dexamethasone. We demonstrated the biphasic effects of exogenous glucocorticoid on osteoblastic mitochondrial functions and elevated intracellular oxidative stress in a dose- and time-dependent manner. On comparison, similar treatment did not induce mitochondrial dysfunctions and oxidative stress in osteoclasts. The production of reactive oxygen/nitrogen species was decreased in osteoclasts. The differences are not due to varying efficiency of cellular antioxidant system. The opposite effects on nitrogen oxide synthase might provide an explanation, as the expression levels of nos2 gene are suppressed in the osteoclast but elevated in the osteoblast. We further revealed that glucocorticoids have a substantial impact on the osteoblastic mitochondria. Basal respiration rate and ATP production were increased upon 24 h incubation of glucocorticoids. The increase in proton leak and nonmitochondrial respiration suggests a potential source of glucocorticoid-induced oxidative stress. Long-term incubation of glucocorticoids accumulates these detrimental changes and results in cytochrome C release and mitochondrial breakdown, consequently leading to apoptosis in osteoblasts. The mitochondrial alterations might be other sources of glucocorticoid-induced oxidative stress in osteoblasts.


Osteoclasts , Oxidative Stress , Apoptosis , Glucocorticoids , Osteoblasts , Osteocytes
10.
Eur J Trauma Emerg Surg ; 45(6): 973-978, 2019 Dec.
Article En | MEDLINE | ID: mdl-30627733

PURPOSE: Traumatic subclavian vascular injury (TSVI) is rare but often fatal. The precise diagnosis of TSVI remains challenging mainly because of its occult nature, less typical presentations, and being overlooked in the presence of polytrauma. Compared to penetrating injuries, it is even more difficult to identify TSVI in patients who have blunt injuries and no visible bleeding. The risk factors associated with TSVI in patients with thoracic trauma are unclear. The aims of this study were to identify risk factors for TSVI in a cohort of patients with thoracic vascular injuries and to report outcomes after clinical treatment. METHODS: From January 2009 to June 2017, 39586 patients were admitted to our hospital (a level I trauma center) due to trauma, and 136 patients with thoracic vascular injury were enrolled in this study. We retrospectively reviewed data from medical records including demographic characteristics, injury scoring systems (RTS, ISS, NISS, TRISS and AIS), management and outcomes. Patients were further divided into the TSVI group (patients with TSVI) and the non-TSVI group (patients with thoracic vascular injuries other than TSVI). Univariate and multivariate analyses were used to identify independent risk factors. RESULTS: The enrolled 136 patients suffered mostly from blunt trauma (89.0%) and 22 of them had TSVI. When compared to the non-TSVI group, the TSVI group had lower Glasgow Coma Scale (GCS) scores (p = 0.002; especially GCS ≤ 12), less concurrent abdominal injury (p < 0.001), lower Injury Severity Scales (ISS) (p = 0.007) and New Injury Severity Scales (NISS) (p < 0.002) but had higher Abbreviated Injury Scales (AIS) of the head ≥ 3 (p = 0.009) and rates of clavicular or scapular fractures (p = 0.013). No difference was detected between the two groups with regard to age, gender, trauma mechanism, vital signs on arrival, or rate of facial and extremities injury. In multivariate regression analyses, GCS ≤ 12, AIS of the head ≥ 3 and the presence of clavicular or scapular fractures were independent risk factors for TSVI (p = 0.026, p = 0.043 and p = 0.005, respectively) after adjustment for confounding factors. Open and endovascular repair were two surgical procedures utilized for these TSVI patients with an overall mortality rate of 18.2%. No difference was found between these groups with regard to mortality rate and the length of ICU stay, but the patients in the TSVI group had a shorter length of hospital stay. CONCLUSIONS: Our results suggest that GCS ≤ 12, AIS of the head ≥ 3 and the presence of clavicular or scapular fractures were independent risk factors for TSVI in patients with thoracic vascular injuries. For patients with thoracic trauma, TSVI should be considered for prompt management when patients exhibit concurrent injuries to the head, clavicle or scapula.


Endovascular Procedures , Subclavian Artery/injuries , Subclavian Vein/injuries , Tertiary Care Centers/statistics & numerical data , Trauma Centers/statistics & numerical data , Vascular System Injuries/diagnosis , Adult , Endovascular Procedures/methods , Endovascular Procedures/statistics & numerical data , Female , Glasgow Coma Scale , Humans , Injury Severity Score , Male , Multiple Trauma/epidemiology , Multiple Trauma/surgery , Prognosis , Retrospective Studies , Risk Factors , Subclavian Artery/surgery , Subclavian Vein/surgery , Treatment Outcome , Vascular System Injuries/etiology , Vascular System Injuries/mortality , Vascular System Injuries/surgery , Wounds, Nonpenetrating/diagnosis
11.
Am J Emerg Med ; 37(4): 603-607, 2019 04.
Article En | MEDLINE | ID: mdl-29941322

BACKGROUND: Conventionally, pelvic fracture-related acute retroperitoneal hemorrhage (ARH) is life threatening and difficult to control. However, the use of angioembolization to treat fracture-associated ARH improves the hemodynamic stability of patients with pelvic fractures. The role of angioembolization in the management of patients with pelvic fracture-related ARH was examined. MATERIALS AND METHODS: We retrospectively reviewed a large case series of patients with pelvic fractures between January 2010 and December 2014. Comparisons were made between patients with and without ARH. In addition, the characteristics of mortality were delineated, whereas the causes of death in patients with pelvic fracture were discussed and analyzed. RESULTS: A total of 1070 patient records were reviewed during the 60-month study period, and the overall mortality rate of pelvic fracture was 7.7% (82/1070). However, there were only seven patients who died due to uncontrolled ARH (0.7%). The patients with ARH had more injuries to other organs than did the patients without ARH (head: 79.7% vs. 31.7%, p < 0.001; chest: 50.3% vs. 10.9%, p < 0.001; abdomen: 72.0% vs. 22.7%, p < 0.001; spine: 12.6% vs. 4.4%, p < 0.001; extremities: 69.2% vs. 44.3%, p < 0.001). CONCLUSION: The treatment for pelvic fracture patients declared dead upon arrival remains limited. However, pelvic fracture-related ARH could be controlled effectively with angioembolization. In addition to ARH, injuries to other organs may play a key role in the mortality of patients with pelvic fractures.


Embolization, Therapeutic/methods , Fractures, Bone/therapy , Hemorrhage/therapy , Pelvic Bones/injuries , Adult , Female , Fractures, Bone/mortality , Hemorrhage/etiology , Humans , Injury Severity Score , Male , Middle Aged , Retroperitoneal Space/pathology , Retrospective Studies , Taiwan , Trauma Centers , Young Adult
12.
In Vivo ; 32(6): 1533-1540, 2018.
Article En | MEDLINE | ID: mdl-30348713

BACKGROUND/AIM: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive types of digestive cancer. Recurrence within one year after surgery is inevitable in most PDAC patients. Recently, cluster of differentiation 44 (CD44) has been shown to be associated with tumor initiation, metastasis and prognosis. This study aimed to explore the correlation of CD44 expression with clinicopathological factors and the role of CD44 in predicting early recurrence (ER) in PDAC patients after radical surgery. MATERIALS AND METHODS: PDAC patients who underwent radical resection between January 1999 and March 2015 were enrolled in this study. Tumor recurrence within 6 months after surgery was defined as ER. Immunohistochemical staining was performed with anti-CD44 antibodies. The association between clinicopathological parameters and CD44 expression was analyzed. Predictors for ER were also assessed with univariate and multivariate analyses. RESULTS: Overall, 155 patients were included in this study. Univariate analysis revealed CA19-9 levels (p=0.014), CD44 histoscores (H-scores; p=0.002), differentiation (p=0.010), nodal status (p=0.005), stage (p=0.003), vascular invasion (p=0.007), lymphatic invasion (p<0.001) and perineural invasion (p=0.042) as risk factors for ER. In multivariate analysis, high CA19-9 levels and CD44 H-scores and poor differentiation independently predicted ER. CONCLUSION: High CA19-9 levels, CD44 H-scores and poor differentiation are independent predictors for ER in PDAC patients undergoing radical resection. Therefore, the determination of CD44 expression might help in identifying patients at a high risk of ER for more aggressive treatment after radical surgery.


Antigens, Tumor-Associated, Carbohydrate/genetics , Carcinoma, Pancreatic Ductal/genetics , Hyaluronan Receptors/genetics , Neoplasm Recurrence, Local/genetics , Aged , Biomarkers, Tumor/genetics , Carcinoma, Pancreatic Ductal/epidemiology , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/surgery , Female , Humans , Kaplan-Meier Estimate , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Prognosis , Risk Factors
13.
Sci Rep ; 8(1): 14612, 2018 10 02.
Article En | MEDLINE | ID: mdl-30279434

Expanding bile leaks after blunt liver trauma require more aggressive treatment than contained bile leaks. In this retrospective study approved by institution review board, we analyzed if non-invasive contrast-enhanced magnetic resonance cholangiography (CEMRC) using hepatocyte-specific contrast agent (gadoxetic acid disodium) could detect and characterize traumatic bile leaks. Between March 2012 and December 2014, written informed consents from 22 included patients (17 men, 5 women) with a median age of 24.5 years (IQR 21.8, 36.0 years) were obtained. Biliary tree visualization and bile leak detection on CEMRC acquired at 10, 20, 30, 90 minutes time points were independently graded by three radiologists on a 5-point Likert scale. Intraclass Correlation (ICC) was computed as estimates of interrater reliability. Accuracy was measured by area under receiver operating characteristic curves (AUROC). Biliary tree visualization was the best on CEMRC at 90 minutes (score 4.30) with excellent inter-rater reliability (ICC = 0.930). Of 22 CEMRC, 15 had bile leak (8 expanding, 7 contained). The largest AUROC of bile leak detection by three radiologists were 0.824, 0.914, 0.929 respectively on CEMRC at 90 minutes with ICC of 0.816. In conclusion, bile leaks of blunt liver trauma can be accurately detected and characterized on CEMRC.


Bile Ducts/diagnostic imaging , Cholangiography/methods , Liver/diagnostic imaging , Magnetic Resonance Imaging/methods , Wounds, Nonpenetrating/diagnostic imaging , Adult , Area Under Curve , Bile Ducts/injuries , Cholangiography/instrumentation , Contrast Media/administration & dosage , Female , Gadolinium DTPA/administration & dosage , Humans , Liver/injuries , Magnetic Resonance Imaging/instrumentation , Male , Observer Variation , ROC Curve , Reproducibility of Results , Retrospective Studies , Wounds, Nonpenetrating/pathology
14.
Am Surg ; 84(6): 1015-1021, 2018 Jun 01.
Article En | MEDLINE | ID: mdl-29981641

Acute surgical abdomen is commonly encountered in the ED and CT is widely used as an informative diagnostic tool to evaluate potential surgical indications. However, the adverse effects of contrast material used in CT scanning have been documented. We sought to delineate the role of noncontrast CT in the evaluation of patients with acute surgical abdomen. Between August 2015 and December 2015, patients with nontraumatic surgical abdomen who underwent preoperative CT were enrolled in the current study. The patients for whom the CT results permitted surgical decision-making were the focus of this study. The disease entities included acute appendicitis, acute cholecystitis, hollow organ perforation, mechanical bowel obstruction, intra-abdominal abscess that could not be drained percutaneously, and ischemic bowel disease. The results of contrast-enhanced and noncontrast CT were compared and analyzed. The surgical conditions identifiable by noncontrast CT were recorded. In total, 227 patients were enrolled in the study. In 90.7 per cent of patients overall, the findings indicating the need for surgical treatment were visualized on both the noncontrast and contrast-enhanced images (acute appendicitis: 89.3%, acute cholecystitis: 89.7%, hollow organ perforation: 97.4%, bowel obstruction: 100%, intra-abdominal abscess: 100%, and ischemic bowel disease: 55.6%). Noncontrast CT provides benefit for critical decision-making. Body mass index may affect the accuracy of noncontrast imaging in the evaluation of patients with surgical abdomen. In some specific situations, contrast enhancement remains necessary.


Abdomen, Acute/diagnostic imaging , Abdomen, Acute/surgery , Gastrointestinal Diseases/diagnostic imaging , Gastrointestinal Diseases/surgery , Tomography, X-Ray Computed , Abdomen, Acute/etiology , Adult , Aged , Clinical Decision-Making , Contrast Media , Emergency Service, Hospital , Female , Gastrointestinal Diseases/complications , Humans , Male , Middle Aged , Patient Selection , Retrospective Studies
15.
Sci Rep ; 8(1): 6213, 2018 04 18.
Article En | MEDLINE | ID: mdl-29670226

Open abdomen indicates the abdominal fascia is unclosed to abbreviate surgery and to reduce physiological stress. However, complications and difficulties in patient care are often encountered after operation. During May 2008 to March 2013, we performed a prospective protocol-directed observation study regarding open abdomen use in trauma patients. Bogota bag is the temporary abdomen closure initially but negative pressure dressing is used later. A goal-directed ICU care is applied and primary fascial closure is the primary endpoint. There were 242 patients received laparotomy after torso trauma and 84 (34.7%) had open abdomen. Twenty patients soon died within one day and were excluded. Among the included 64 patients, there were 49 (76.6%) males and the mean Injury Severity Score was 31.7. Uncontrolled bleeding was the major indication for open abdomen (64.1%) and the average duration of open abdomen was about 4.2 ± 2.2 days. After treatment, 53(82.8%) had primary fascia closure, which is significant for patient survival (odds ratio 21.6; 95% confidence interval: 3.27-142, p = 0.0014). Factors related to failed primary fascia closure are profound shock during operation, high Sequential Organ Failure Assessment Score in ICU and inadequate urine amount at first 48 hours admission.


Abdomen/surgery , Fascia , Torso/injuries , Torso/surgery , Wound Closure Techniques , Wounds and Injuries/mortality , Wounds and Injuries/surgery , Adult , Fasciotomy , Female , Humans , Male , Middle Aged , Odds Ratio , Prognosis , Treatment Outcome , Wounds and Injuries/diagnosis , Young Adult
16.
Am J Emerg Med ; 36(11): 1937-1942, 2018 11.
Article En | MEDLINE | ID: mdl-29486990

INTRODUCTION: Managing patients with open pelvic fractures continues to be challenging and requires a multidisciplinary approach. In this study, we examined the characteristics of patients with open pelvic fractures and strategies for managing such patients. MATERIALS AND METHODS: The records of patients with open pelvic fractures from January 2010 to August 2016 were retrospectively reviewed. Emergency surgery was performed to control hemorrhaging in patients with an active external hemorrhage. Transcatheter arterial embolization (TAE) was used for definitive hemostasis. The relation between cause of death and timing of death was examined. We also compared the characteristics of surviving and non-surviving patients. Furthermore, patients who received both surgery and post-operative TAE were analyzed in detail. RESULTS: In total, 42 patients with open pelvic fractures were enrolled in the study. The overall mortality rate among patients with open pelvic fractures was 26.2%. Patients whose deaths were related to hemorrhaging and associated injuries died significantly earlier than patients whose deaths were related to sepsis and multiple organ failure (1.3days vs. 12.3days, p<0.001). Sixteen patients (38.1%) received TAE for hemostasis, and their systolic blood pressure (SBP) improved significantly following TAE (from 88.4mmHg to 111.6mmHg, p<0.05). In the patients who received both surgery and post-operative TAE (n=8), the SBP increased significantly after surgery (from 58.8mmHg to 81.1mmHg, p<0.05). Similarly, the patients' SBP after TAE was significantly higher than their post-operative SBP (110.5mmHg vs. 81.1mmHg, p<0.05). CONCLUSION: Active external hemorrhaging was initially controlled when managing patients with open pelvic fractures; however, most patients also required TAE for definitive hemorrhage control. Early TAE should be considered due to the high probability of concomitant internal and external hemorrhage. Close observation and further infection control are important following the hemostatic procedure.


Embolization, Therapeutic/methods , Fractures, Bone/therapy , Hemorrhage/prevention & control , Pelvic Bones/injuries , Accidental Falls/statistics & numerical data , Accidents, Traffic/statistics & numerical data , Adult , Combined Modality Therapy , Emergency Treatment/methods , Female , Fractures, Bone/mortality , Hemorrhage/mortality , Hemostasis, Surgical/methods , Hemostasis, Surgical/mortality , Humans , Male , Treatment Outcome
17.
Burns ; 44(4): 800-806, 2018 06.
Article En | MEDLINE | ID: mdl-29258727

PURPOSE: The Formosa Fun Coast explosion is an internationally-known event that occurred in Taiwan on June 27th, 2015. The blast involved 495 casualties in total, with 253 patients receiving 2nd degree or deeper burns on greater than 40% of the total body surface area (TBSA). Questions were raised regarding whether these victims were sent to the appropriate hospitals or not. Therefore, we analyzed the effect of the initial admission destination in this study. MATERIAL AND METHODS: We retrospectively reviewed all of the victims from the explosion who were sent to the emergency department of Linkou and Keelung Chang Gung Memorial Hospitals. Patients were divided by direct admission and received via transfer. The basic demographics, the efficacy of the initial resuscitation and the clinical outcomes were analyzed. RESULTS: In total, forty-six patients were included. Thirty-five of them were primarily admitted, and eleven of them were received via transfer. Between the two groups, there was no significant difference in the resuscitation outcome. The ratio of delaying intubation was similar (14.3% vs 27.3%, p=0.322). The rate of delayed-detected ischemic events was significantly increased in the referral group (0% vs 27.3%, p=0.001). However, there was no amputation event in either group. No difference in mortality was observed between groups (5.7% vs 9.1%, p=0.692). CONCLUSION: Our preliminary findings suggest that local hospitals are capable of providing high-quality acute care to mass casualty burn victims. Our results suggest that patients with suspected limb ischemia should be rapidly transferred to a regional burn center to ensure optimal care. Systemic pre-planning such as employing telemedicine and personnel collaboration, should be considered by the administration to maximize the function of preliminary hospitals in burn care.


Burn Units , Burns/therapy , Delayed Diagnosis/statistics & numerical data , Explosions , Hospitals , Ischemia/diagnosis , Mass Casualty Incidents , Patient Transfer/statistics & numerical data , Resuscitation/statistics & numerical data , Adolescent , Adult , Body Surface Area , Emergency Service, Hospital , Extremities/blood supply , Female , Hospitalization , Humans , Intubation, Intratracheal/statistics & numerical data , Male , Referral and Consultation/statistics & numerical data , Retrospective Studies , Taiwan , Young Adult
18.
Asian J Surg ; 41(2): 115-123, 2018 Mar.
Article En | MEDLINE | ID: mdl-28010955

OBJECTIVE: Pancreatic ductal adenocarcinoma is one of the most malignant types of cancer. This study evaluated the 3-year and 5-year surgical outcomes associated with the cancer and determined whether statistically identified factors can be used to predict survival. METHODS: This retrospective review was conducted from 1995 to 2010. Patients who had resectable pancreatic ductal adenocarcinoma and received surgical treatment were included. Cases of hospital mortality were excluded. The relationships between several clinicopathological factors and the survival rate were analyzed. RESULTS: A total of 223 patients were included in this study. The 3-year and 5-year survival rates were 21.4% and 10.1%, respectively, and the median survival was 16.1 months. Tumor size, N status, and resection margins were independent predictive factors for 3-year survival. Tumor size independently predicted 5-year survival. CONCLUSION: Tumor size is the most important independent prognostic factor for 3-year and 5-year survival. Lymph node status and the resection margins also independently affected the 3-year survival. These patient outcomes might be improved by early diagnosis and radical resection. Future studies should focus on the tumor biology of this aggressive cancer.


Carcinoma, Pancreatic Ductal/mortality , Carcinoma, Pancreatic Ductal/surgery , Cause of Death , Pancreatectomy/methods , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/surgery , Academic Medical Centers , Carcinoma, Pancreatic Ductal/pathology , Cohort Studies , Disease-Free Survival , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Multivariate Analysis , Neoplasm Invasiveness/pathology , Neoplasm Staging , Pancreatectomy/mortality , Pancreatic Neoplasms/pathology , Retrospective Studies , Risk Assessment , Statistics, Nonparametric , Survival Analysis , Taiwan , Time Factors , Treatment Outcome
19.
Oncotarget ; 8(56): 95596-95605, 2017 Nov 10.
Article En | MEDLINE | ID: mdl-29221152

Comparable failure rates of distal or proximal transcatheter arterial embolization (TAE) techniques for blunt splenic injuries have been reported. This study is to investigate the efficacy and complication of combining both TAE techniques. We included 26 patients of blunt splenic injuries for TAE therapy and randomized them into distal TAE and combined TAE groups. A prospective study was performed to compare their demographics, clinical parameters, hemograms, post-TAE splenic infarct volumes, splenic abscess and pancreatitis between the two groups. Of 26 patients, 17 received distal TAE, 9 received combined TAE. Their basic demographics, clinical parameters and hemograms did not differ. Mean systolic blood pressure of all patients was significantly elevated after TAE at 24 hours later. Three patients of distal TAE group had residual pseudoaneurysms in follow up. They were considered failures in distal TAE group as opposed to all successes in combined TAE group. The risk difference of failure of distal TAE was 17.6%. None developed post-TAE splenic abscess, massive splenic infarct or pancreatitis. The mean splenic infarct volume of distal TAE (10.9%) versus combined TAE groups (6.6%) was not significant (p = 0.481). Combined TAE is effective and safe to decrease the failure rates of non-operative management for blunt splenic injuries.

20.
Surg Endosc ; 31(10): 4201-4210, 2017 10.
Article En | MEDLINE | ID: mdl-28281124

BACKGROUND: To evaluate the management and outcomes of blunt pancreatic injuries based on the integrity of the major pancreatic duct (MPD). METHODS: Between August 1996 and August 2015, 35 patients with blunt pancreatic injuries underwent endoscopic retrograde pancreatography (ERP). Medical charts were retrospectively reviewed for demography, ERP timing, imaging findings, management, and outcome. RESULTS: Of the 35 patients, 21 were men and 14 were women, with ages ranging from 11 to 70 years. On the basis of the ERP findings, we propose a MPD injury classification as follows: class 1 indicates normal MPD; class 2, partial injury with intact MPD continuity; and class 3, complete injury with disrupted MPD continuity. Both classes 2 and 3 are subdivided into classes a, b, and c, which represent the pancreatic tail, body, and head, respectively. In this report, 14 cases belonged to class 1, 10 belonged to class 2, and 11 belonged to class 3. Of the 14 patients with class 1 injuries, 10 underwent nonsurgical treatment and 4 underwent pancreatic duct stenting. Of the 10 patients with class 2 injuries, 4 underwent nonsurgical treatment and 6 underwent pancreatic duct stenting. Two of the 11 patients with class 3 injuries underwent pancreatic duct stenting; one in the acute stage developed sepsis that led to death even after converting to distal pancreatectomy plus splenectomy. Of the 11 patients with class 3 injuries, spleen-preserving distal pancreatectomy was performed in 6, distal pancreatectomy plus splenectomy in 2, and Roux-en-Y pancreaticojejunostomy after central pancreatectomy in 2. The overall pancreatic-related morbidity rate was 60% and the mortality rate was 2.8%. CONCLUSION: Based on our experience, class 1 and 2 injuries could be treated by nonsurgical means and pancreatic duct stenting could be an adjunctive therapy in class 2b and 2c injuries. Operation is warranted in class 3 injuries.


Abdominal Injuries/diagnostic imaging , Cholangiopancreatography, Endoscopic Retrograde , Pancreas/diagnostic imaging , Pancreatic Ducts/diagnostic imaging , Wounds, Nonpenetrating/diagnostic imaging , Abdominal Injuries/surgery , Adolescent , Adult , Aged , Child , Cholangiopancreatography, Endoscopic Retrograde/methods , Female , Humans , Male , Middle Aged , Pancreas/injuries , Pancreas/surgery , Pancreatectomy , Pancreatic Ducts/injuries , Pancreatic Ducts/surgery , Reference Values , Retrospective Studies , Treatment Outcome , Wounds, Nonpenetrating/surgery , Young Adult
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